title: The novel hypothesis of carcinogenesis and anti-cancer treatment perspectives - Hydroxyethylthiamine diphosphate.
abstract: In presented article, the novel hypothesis of carcinogenesis, and thorough discussion of some essential biochemical mechanisms which might be responsible for the malignant transformation of cells (bond disorders between Fe(3+) and S(+)-methionine in cytochrome; blockage of the last 3-d orbital of Fe by the certain ligand and formation of 6th coordinated bond leading to Fe(3+) reduction up to Fe(2+) and cessation of tissue respiration; increase in mitochondrial pH and further in cell, leading to decreased activity of most of enzymes (thiamine diphosphate, oxidases); formation of S-adenosyl-methionine with its further dissociation and production of adenosine and homocysteine; effects of homocysteine on DNA structures, homocysteine-induced dimethylation of certain nitrogen basis and their extrusion from strands of DNA leading to mutations and cellular atypism) has been suggested. Along with theoretical discussions, article provides results of preliminary investigations carried out on C57Bl/6J mice with Ehrlich carcinoma aimed to capture lipoic acid amide with Hydroxyethylthiamine diphosphate, and study effects of Hydroxyethylthiamine diphosphate against malignant transformation of cells. Experiments have shown inhibition of cancer growth in treated animals. Morphological investigations of cancer tissue revealed necrotic zones, inflammatory infiltrations, central necrosis with adjacent inflammatory mono- and polymorph infiltrations, must cells, segmento-nuclear leukocytes, lymphadenoid follicular hyperplasia. According to the novel hypothesis of carcinogenesis and results of experiments the new approaches and perspectives of anti-cancer treatment with the use of Hydroxiethyl-thiamine diphosphate has been suggested.
authors.affiliation: Oncology National Center, Tbilisi State Medical University.
authors.forename: L
authors.initials: L
authors.lastname: Gevorkian
authors.forename: K
authors.initials: K
authors.lastname: Gambashidze
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D063646:Carcinogenesis / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010119:Oxythiamine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010119:Oxythiamine; C008030:hydroxyethylthiamine